Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28914 | 86965;86966;86967 | chr2:178559392;178559391;178559390 | chr2:179424119;179424118;179424117 |
| N2AB | 27273 | 82042;82043;82044 | chr2:178559392;178559391;178559390 | chr2:179424119;179424118;179424117 |
| N2A | 26346 | 79261;79262;79263 | chr2:178559392;178559391;178559390 | chr2:179424119;179424118;179424117 |
| N2B | 19849 | 59770;59771;59772 | chr2:178559392;178559391;178559390 | chr2:179424119;179424118;179424117 |
| Novex-1 | 19974 | 60145;60146;60147 | chr2:178559392;178559391;178559390 | chr2:179424119;179424118;179424117 |
| Novex-2 | 20041 | 60346;60347;60348 | chr2:178559392;178559391;178559390 | chr2:179424119;179424118;179424117 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/V | rs786205373  |
-0.909 | None | N | 0.096 | 0.048 | 0.128392430309 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.87E-06 | 0 |
| I/V | rs786205373 |
-0.909 | None | N | 0.096 | 0.048 | 0.128392430309 | gnomAD-4.0.0 | 2.05281E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.6987E-06 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.231 | likely_benign | 0.2842 | benign | -1.744 | Destabilizing | 0.007 | N | 0.275 | neutral | None | None | None | None | N |
| I/C | 0.573 | likely_pathogenic | 0.6331 | pathogenic | -0.767 | Destabilizing | 0.356 | N | 0.452 | neutral | None | None | None | None | N |
| I/D | 0.6397 | likely_pathogenic | 0.7234 | pathogenic | -1.329 | Destabilizing | 0.072 | N | 0.543 | neutral | None | None | None | None | N |
| I/E | 0.5845 | likely_pathogenic | 0.657 | pathogenic | -1.195 | Destabilizing | 0.072 | N | 0.511 | neutral | None | None | None | None | N |
| I/F | 0.1541 | likely_benign | 0.1785 | benign | -0.996 | Destabilizing | None | N | 0.136 | neutral | N | 0.440692809 | None | None | N |
| I/G | 0.4791 | ambiguous | 0.5791 | pathogenic | -2.183 | Highly Destabilizing | 0.072 | N | 0.478 | neutral | None | None | None | None | N |
| I/H | 0.4904 | ambiguous | 0.5517 | ambiguous | -1.543 | Destabilizing | 0.628 | D | 0.517 | neutral | None | None | None | None | N |
| I/K | 0.4944 | ambiguous | 0.5839 | pathogenic | -1.017 | Destabilizing | 0.072 | N | 0.507 | neutral | None | None | None | None | N |
| I/L | 0.1022 | likely_benign | 0.1176 | benign | -0.541 | Destabilizing | None | N | 0.097 | neutral | N | 0.432726686 | None | None | N |
| I/M | 0.0955 | likely_benign | 0.11 | benign | -0.37 | Destabilizing | 0.171 | N | 0.445 | neutral | N | 0.456046263 | None | None | N |
| I/N | 0.2103 | likely_benign | 0.2745 | benign | -1.072 | Destabilizing | 0.171 | N | 0.538 | neutral | N | 0.446597274 | None | None | N |
| I/P | 0.6757 | likely_pathogenic | 0.7766 | pathogenic | -0.916 | Destabilizing | 0.356 | N | 0.54 | neutral | None | None | None | None | N |
| I/Q | 0.4624 | ambiguous | 0.5439 | ambiguous | -1.06 | Destabilizing | 0.356 | N | 0.519 | neutral | None | None | None | None | N |
| I/R | 0.4013 | ambiguous | 0.4748 | ambiguous | -0.683 | Destabilizing | 0.214 | N | 0.531 | neutral | None | None | None | None | N |
| I/S | 0.1862 | likely_benign | 0.2441 | benign | -1.764 | Destabilizing | 0.029 | N | 0.439 | neutral | N | 0.402577138 | None | None | N |
| I/T | 0.1457 | likely_benign | 0.1936 | benign | -1.506 | Destabilizing | None | N | 0.181 | neutral | N | 0.404385292 | None | None | N |
| I/V | 0.0549 | likely_benign | 0.0596 | benign | -0.916 | Destabilizing | None | N | 0.096 | neutral | N | 0.390149345 | None | None | N |
| I/W | 0.7787 | likely_pathogenic | 0.8103 | pathogenic | -1.289 | Destabilizing | 0.864 | D | 0.525 | neutral | None | None | None | None | N |
| I/Y | 0.4671 | ambiguous | 0.5071 | ambiguous | -0.955 | Destabilizing | 0.038 | N | 0.467 | neutral | None | None | None | None | N |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.